Central Nervous System Agents in Medicinal Chemistry, 2010, 10, 91-96 91 1871-5249/10 $55.00+.00 © 2010 Bentham Science Publishers Ltd. Migraine and Coronary Artery Disease: An Open Study on the Genetic Polymorphism of the 5, 10 Methylenetetrahydrofolate (MTHFR) and Angiotensin I-Converting Enzyme (ACE) Genes V. Pizza 1 , A. Bisogno 2 , E. Lamaida 3 , A. Agresta 1 , G. Bandieramonte 4 , A. Volpe 4 , R. Galasso 4 , L. Galasso 4 , M.Caputo 2 , M.F. Tecce 2 and A. Capasso 2,* 1 Neurophysiopathology, 3 Neurosurgery and 4 Neuroradiology Unit, S. Luca Hospital, Vallo della Lucania (Sa), 2 Department of Pharmaceutical Science, University of Salerno, Italy Abstract: Genetic factors that increase susceptibility to oxidative stress, endothelial disfunction and, possibly, stroke in- clude angiotensin-converting enzyme gene deletion polymorphism (ACE-DD) and the methylentetrahydropholate reduc- tase (MTHFR) C677-TT polymorphism. The relationship of ACE-DD genotype to ischemic stroke and cardiovascular disease is controversial, but it has been independently linked to lacunar infarction, in the absence of carotid atheroma. Lea et al. (2005) reported that the ACE DD genotype acts in combination with the MTHFR T/T genotype to increase migraine susceptibility, with the greatest effect in those with aura. The “TT” polymorphism is also associated with an increased risk of migraine with aura, independent of other cardiovascular risk factors. The aim of our study was to evaluate the incidence of ACE and MTHFR genes polymorphisms in a consecutive series of migrainous patients and of patients affected by myocardial infarction. We studied a series of 103 migrainous patients (1), whose age was between 13 and 75 years (81 suffering from migraine without aura, MwA, 9 from migraine with aura, MWA, 13 from mixed forms MwA-MWA, ac- cording to ICHD-II 2004 criteria) and of 336 patients (2) suffering from ischaemic cardiopathy (myocardial infarction, MI). The analysis, based on Polymerase Chain Reaction (PCR) and on reverse-hybridization, showed as follows: MTHFR (C677T): 60 patients (58%) (1) and 186 (56%) (2) were heterozygous; 9 patients (9%) (1) and 54 (16%) (2) were mutated. The result of 1patient (2) was unknown. MTHFR (A1298C): 54 patients (52%) (1) and 146 (44%) (2) were heterozygous, 7 patients (7%) (1) and 33 (10%) (2) were mutated. The result of 1 patient (2) was unknown. ACE (evaluated on 101 patients (1) and 245 (2)): 45patients (43%) (1) and 133 (54%) (2) had an ID genotype; 42 (41%) (1) and 87 (36%) (2) had a DD genotype. The results of our study confirm the high incidence in the genetic polymorphisms ACE and MTHFR in migraineuse. These data are confirmed in the sample of patients affected by myocardial infarction. This gives evidence of a strong rela- tionship between migraine and major vascular diseases and let us hypothesize an important role of ACE and MTHFR sys- tem in the pathogenetic model of migraine for its capability to interfere with the endothelial regulation tone. Once an ef- fective role in the genesis of migraine and in the increased risk of migrainous patients to evolve into an ischemic pathol- ogy has been obviously assigned to this genetic mutation, future researches must aim through wider and more controlled casistics also to clarify the role that drugs acting on these systems may have on the resolution of these diseases. Keywords: Migraine, polymorphism, stroke. INTRODUCTION The possible relationship between migraine and ischae- mic stroke risk is an important public health concern, but the mechanism underlying this relationship is complex and not fully clear. Migraine and stroke can coexist: stroke may oc- cur with the clinical features of migraine, or it may be in- duced by migraine. In the last case, a prolonged migraine aura may induce a condition called “true migrainous infarc- tion” [1]. *Address correspondence to this author at the Department of Pharmaceuti- cal Science, University of Salerno, Italy; Tel:/Fax: +39-089-969744; E-mail: annacap@unisa.it There are good epidemiological evidences about the rela- tionship of migraine not only with an increased risk of stroke (which is stronger in young adults, but may persist in the elderly) but also with any vascular ischaemic event, myocar- dial infarction included [2]. The exact mechanism by which migraine with aura may lead to ischaemic vascular events is still unknown and probably very complex. Prospective data give no evidence that migraine without aura is associated with increate risk of any ischaemic vascular events [2]. Several studies showed an increased risk of stroke in people suffering from migraine, some others failed in finding this association. The probable mechanism is thought to be